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Background & Aims: Early identification of worsening HF enables timely adjustments to prevent hospitalization. Recent studies show the HeartLogic™ algorithm detects congestion and reduces HF events. However, it is unclear which patients benefit most. Therefore, this study aims to identify and characterize HF patients who benefit most from CIED-based remote monitoring with HeartLogic™., Methods: In this multicenter retrospective study, patients with a CIED and HeartLogic™ algorithm under structured follow-up were included. Patients were classified as having "substantial benefit" or "no benefit" from monitoring., Results: In total, 242 patients were included (male n = 190, 79%, median age 61 years [IQR 61-77]). Median follow-up was 1.2 years [IQR 1.1-2.7]. Among 378 alerts, 266 were true positive (70%) and 112 false positive (30%). Of the 242 patients, 69 (29%) were classified as having "substantial benefit", while 173 (71%) had "no benefit" from HeartLogic™ monitoring. Univariate and multivariate analysis showed that patients with "substantial benefit" had higher NYHA functional class (OR 2.64, P = 0.004), higher NT-ProBNP (OR 1.02, P = 0.003), higher serum creatinine (OR 1.10, P < 0.001), lower LVEF (OR 1.19, P = 0.004), more severe mitral regurgitation (OR 2.16, P = 0.006), higher right ventricular end diastolic volume (OR 1.05, P = 0.040), higher pulmonary artery pressures (OR 1.19, P = 0.003), and were more likely to use loop diuretics (OR 2.79, P = 0.001). Among patients with "substantial benefit," the positive predictive value (PPV) of HeartLogic™ to detect congestion was 92%., Conclusion: The utilization of CIED-based HeartLogic™ driven HF care demonstrated pronounced efficacy, predominantly in patients exhibiting characteristics of HF at a more advanced disease stage., Competing Interests: Declaration of competing interest The department of Cardiology of the LUMC reports receiving unrestricted research and educational grants from Boston Scientific Corporation, Medtronic, and Biotronik. The department of cardiology of OLV Aalst reports receiving research and educational grants from Boston Scientific, Medtronic, Biotronik, Abbott St Jude Medical, and Microport and an educational and research grant from Boston Scientific with reference number ISRRM11793. The funders were not involved in study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. ADE receives consultancy and speaker fees from Boston Scientific Corporation and Medtronic. SLMAB receives speaker fees from Boston Scientific Corporation and Medtronic. The other authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Pharmacological options for patients with a failing systemic right ventricle (RV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are not well defined. This study aims to investigate the feasibility and effects of sacubitril/valsartan treatment in a single-centre cohort of patients., Methods: Data on all consecutive adult patients (n=20, mean age 46 years, 50% women) with a failing systemic RV in a biventricular circulation treated with sacubitril/valsartan in our centre are reported. Patients with a systemic RV ejection fraction of ≤35% who were symptomatic despite treatment with β-blocker and ACE-inhibitor/angiotensin II receptor-blockers were started on sacubitril/valsartan. This cohort underwent structural follow-up including echocardiography, exercise testing, laboratory investigations and quality of life (QOL) assessment., Results: Six-month follow-up data were available in 18 out of 20 patients, including 12 (67%) patients with TGA after atrial switch and 6 (33%) patients with ccTGA. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) decreased significantly (950-358 ng/L, p<0.001). Echocardiographic systemic RV fractional area change and global longitudinal strain showed small improvements (19%-22%, p<0.001 and -11% to -13%, p=0.014, respectively). The 6 min walking distance improved significantly from an average of 564 to 600 m (p=0.011). The QOL domains of cognitive function, sleep and vitality improved (p=0.015, p=0.007 and p=0.037, respectively)., Conclusions: We describe the first patient cohort with systemic RV failure treated with sacubitril/valsartan. Treatment appears feasible with improvements in NT-pro-BNP and echocardiographic function. Our positive results show the potential of sacubitril/valsartan for this patient population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Aims: The implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator-based HeartLogic™ algorithm has recently been developed for early detection of impending decompensation in heart failure (HF) patients; but whether this novel algorithm can reduce HF hospitalizations has not been evaluated. We investigated if activation of the HeartLogic algorithm reduces the number of hospital admissions for decompensated HF in a 1 year post-activation period as compared with a 1 year pre-activation period., Methods and Results: Heart failure patients with an implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator with the ability to activate HeartLogic and willingness to have remote device monitoring were included in this multicentre non-blinded single-arm trial with historical comparison. After a HeartLogic alert, the presence of HF symptoms and signs was evaluated. If there were two or more symptoms and signs apart from the HeartLogic alert, lifestyle advices were given and/or medication was adjusted. After activation of the algorithm, patients were followed for 1 year. HF events occurring in the 1 year prior to activation and in the 1 year after activation were compared. Of the 74 eligible patients (67.2 ± 10.3 years, 84% male), 68 patients completed the 1 year follow-up period. The total number of HF hospitalizations reduced from 27 in the pre-activation period to 7 in the post-activation period (P = 0.003). The number of patients hospitalized for HF declined from 21 to 7 (P = 0.005), and the hospitalization length of stay diminished from average 16 to 7 days (P = 0.079). Subgroup analysis showed similar results (P = 0.888) for patients receiving cardiac resynchronization therapy during the pre-activation period or not receiving cardiac resynchronization therapy, meaning that the effect of hospitalizations cannot solely be attributed to reverse remodelling. Subanalysis of a single-centre Belgian subpopulation showed important reductions in overall health economic costs (P = 0.025)., Conclusion: Activation of the HeartLogic algorithm enables remote monitoring of HF patients, coincides with a significant reduction in hospitalizations for decompensated HF, and results in health economic benefits., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: Patients undergoing heart failure surgery are at risk for developing postoperative vasoplegia. The aim of this study was to determine the incidence, survival, and predictors of vasoplegia in heart failure patients undergoing mitral valve repair for functional mitral regurgitation and to evaluate the effect of ischemic versus non-ischemic etiology., Design: Retrospective., Setting: University medical center, single institutional., Participants: Heart failure patients with functional mitral regurgitation who underwent restrictive mitral annuloplasty (2006-2015)., Measurements and Main Results: One hundred twenty-two patients were included (48% ischemic etiology). The incidence of vasoplegia was 19% and was not influenced by mitral regurgitation etiology. Ninety-day survival rate was decreased in vasoplegic compared with non-vasoplegic patients (65% v 93%, p < 0.001). After adjusting for age, gender, and heart failure etiology, prior hypertension (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.08-0.91; p = 0.034), higher creatinine clearance (OR 0.97; 95% CI 0.95-0.99; p = 0.009), and beta-blocker use (OR 0.25; 95% CI 0.09-0.73; p = 0.011) decreased the risk of vasoplegia. Anemia (OR 3.00; 95% CI 1.10-8.20; p = 0.032) and longer cross clamp (OR 1.03; 95% CI 1.01-1.04; p = 0.001), cardiopulmonary bypass (OR 1.01; 95% CI 1.00-1.02; p = 0.003), and procedure times (OR 1.01; 95% CI 1.00-1.02, p = 0.002) increased the risk of vasoplegia., Conclusions: Vasoplegia occurs in 19% of heart failure patients undergoing mitral valve repair for functional mitral regurgitation. It is associated with a poor early outcome. Prior hypertension, a higher creatinine clearance, and beta-blocker use were associated with a decreased risk of vasoplegia, whereas anemia and longer procedure times were associated with an increased risk of vasoplegia, independent of heart failure etiology., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Vasoplegia is a severe complication which may occur after cardiac surgery, particularly in patients with heart failure. It is a result of activation of vasodilator pathways, inactivation of vasoconstrictor pathways and the resistance to vasopressors. However, the precise etiology remains unclear. The aim of the Vasoresponsiveness in patients with heart failure (VASOR) study is to objectify and characterize the altered vasoresponsiveness in patients with heart failure, before, during and after heart failure surgery and to identify the etiological factors involved., Methods: This is a prospective, observational study conducted at Leiden University Medical Center. Patients with and patients without heart failure undergoing cardiac surgery on cardiopulmonary bypass are enrolled. The study is divided in two inclusion phases. During phase 1, 18 patients with and 18 patients without heart failure are enrolled. The vascular reactivity in response to a vasoconstrictor (phenylephrine) and a vasodilator (nitroglycerin) is assessed in vivo on different timepoints. The response to phenylephrine is assessed on t1 (before induction), t2 (before induction, after start of cardiotropic drugs and/or vasopressors), t3 (after induction), t4 (15 min after cessation of cardiopulmonary bypass) and t5 (1 day post-operatively). The response to nitroglycerin is assessed on t1 and t5. Furthermore, a sample of pre-pericardial fat tissue, containing resistance arteries, is collected intraoperatively. The ex vivo vascular reactivity is assessed by constructing concentrations response curves to various vasoactive substances using isolated resistance arteries. Next, expression of signaling proteins and receptors is assessed using immunohistochemistry and mRNA analysis. Furthermore, the groups are compared with respect to levels of organic compounds that can influence the cardiovascular system (e.g. copeptin, (nor)epinephrine, ANP, BNP, NTproBNP, angiotensin II, cortisol, aldosterone, renin and VMA levels). During inclusion phase 2, only the ex vivo vascular reactivity test is performed in patients with (N = 12) and without heart failure (N = 12)., Discussion: Understanding the difference in vascular responsiveness between patients with and without heart failure in detail, might yield therapeutic options or development of preventive strategies for vasoplegia, leading to safer surgical interventions and improvement in outcome., Trial Registration: The Netherlands Trial Register (NTR), NTR5647. Registered 26 January 2016.

Right ventricular (RV) dysfunction is a well-known prognostic factor in several cardiac diseases. However, the prevalence of RV dysfunction in hypertrophic cardiomyopathy (HC) is unclear and its prognostic value is unknown. This study aims at addressing these issues assessing RV function with speckle tracking echocardiography. In 267 HC patients (52 ± 15 years, 68% male), standard and advanced echocardiographic measurements of RV function were performed including RV 4-chamber longitudinal strain (RV4CLS) and RV free wall longitudinal strain (RVFWLS). The primary end point was all-cause mortality and heart failure development. RV dysfunction was observed in 9% of patients based on tricuspid annular plane systolic excursion (≤17 mm), 5% based on fractional area change (<35%), 23% based on RVFWLS ≥-19%, 39% based on RVFWLS ≥-23%, and 55% based on RV4CLS ≥-20%. In total 59 (22%) patients reached the primary end point during a median follow-up of 6.7 (interquartile range 4.2 to 9.8) years. Kaplan-Meier survival curve showed a significant worse survival free of the end point for patients with impaired RV4CLS ≥-20% versus patients with preserved RV4CLS <-20% (log-rank 7.0, p = 0.008) and for patients with impaired RVFWLS ≥-19% versus patients with preserved RVFWLS <-19% (log-rank 4.4, p = 0.037). Multivariable Cox regression analysis showed that E/E' (hazards ratio [HR] 2.26 [1.30 to 3.92], p = 0.004), left ventricular global longitudinal strain LV GLS (HR 1.08 (1.01 to 1.17), p = 0.034) and RV4CLS (HR 1.08 (1.02 to 1.15), p = 0.007) were independently associated with the primary end point. In conclusion, RV dysfunction as measured by longitudinal strain is relatively frequent in HC patients. Impaired RV4CLS is - together with LV GLS and E/E' - associated with adverse outcome, which may indicate a more severe form of HC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Patients with end-stage renal disease who are undergoing dialysis are reported to be at high risk of sudden cardiac death (SCD), and to date, no therapy has been shown to be effective in reducing this risk. The feasibility and value of prophylactic implantable cardioverter-defibrillator (ICD) implantation to prevent SCD is uncertain., Methods: We conducted the ICD2 trial (Implantable Cardioverter-Defibrillator in Dialysis Patients), a prospective, randomized, controlled study investigating the value and safety of ICD implantation to prevent SCD in 200 patients on dialysis with a left ventricular ejection fraction ≥35%, after adequate screening and optimization of other treatments. The primary end point was SCD. Secondary end points were all-cause mortality and ICD-related complications., Results: The trial was stopped as per the recommendation of the data and safety monitoring board for futility reasons after inclusion of 188 patients, 97 in the ICD group and 91 in the control group. The median duration of follow-up was 6.8 years (interquartile range, 3.8-8.8 years). SCD occurred in 19 of 188 cases (10.1%), 11 of 97 in the ICD group and 8 of 91 in the control group. The cumulative SCD incidence at 5 years was 9.7% (95% CI, 3.3%-16.2%) in the ICD group and 7.9% (95% CI, 1.7-14.0%) in the control group, resulting in a hazard ratio of 1.32 (95% CI, 0.53-3.29; P=0.55). Overall, 99 of 188 patients died (52.7%), 52 in the ICD group and 47 in the control group. Five-year survival probability was 50.6% (95% CI, 39.8%-61.5%) in the ICD group and 54.5% (95% CI, 43.0-66.0%) in the control group, resulting in a hazard ratio of 1.02 (95% CI, 0.69-1.52; P=0.92). Among 80 patients who received an ICD, 25 adverse events related to ICD implantation occurred., Conclusions: In a well-screened and well-treated population undergoing dialysis, prophylactic ICD therapy did not reduce the rate of SCD or all-cause mortality, which remained high., Clinical Trial Registration: URL: http://www.controlled-trials.com . Unique identifier: ISRCTN20479861.

Background: Vasoplegia is a severe complication that can develop after surgical procedures for heart failure. The current study evaluated the effect of vasoplegia on survival, cardiac function, and renal function 2 years after surgical left ventricular restoration (SVR)., Methods: Heart failure patients with a left ventricular ejection fraction (LVEF) of 0.35 or less who underwent SVR in 2006 to 2014 were included. Vasoplegia was defined as the continuous need of vasopressors (norepinephrine ≥0.2 μg · kg -1 · min -1 or terlipressin [any dose], or both) combined with a cardiac index of 2.2 L · min -1 · m -2 or higher for at least 12 consecutive hours, starting within the first 3 days postoperatively. The effect of vasoplegia on mortality, New York Heart Association Functional Classification, LVEF, and creatinine clearance was assessed up to 2 years of follow-up., Results: SVR was performed in 113 patients (80% men), aged 62 ± 10 years, and with an LVEF of 0.25 ± 0.06. Postoperative vasoplegia developed in 23%. Survival was lower in patients with vasoplegia compared with patients without vasoplegia at 6 months (62% vs 90%, p = 0.001) and at 2 years (50% versus 84%, p < 0.001). At the 2-year follow-up, New York Heart Association class and LVEF had improved and were similar in both groups (respectively, p = 0.319 and p = 0.444). Creatinine clearance was lower in patients with vasoplegia compared with patients without vasoplegia 2 years postoperatively (p < 0.001), even after correcting for baseline creatinine clearance (p = 0.009)., Conclusions: Vasoplegia after SVR is associated with decreased survival. Despite an improved and similar cardiac function, renal function was compromised in vasoplegic patients at the 2-year follow-up., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Only few studies aimed at identifying predictors of heart failure (HF) in hypertrophic cardiomyopathy (HC) patients. Furthermore, serial echocardiographic analyses are lacking in these patients and little is known about the natural progression of left ventricular (LV) abnormalities and their association with HF development. Aim of this study was to assess the prognostic value of LV global longitudinal strain (GLS) and other clinical and echocardiographic characteristics for the development of HF in patients with nonobstructive HC; furthermore, changes in echocardiographic parameters over time were correlated with HF development. Echocardiography was performed in 236 HC patients (68% men, age: 50 ± 14 years) at their initial visit and during follow-up (6.5(4.1 to 9.8) years). The end point of new HF development or progression to New York Heart Association class III/IV was noted and echocardiographic changes over time were compared among patients with and without HF using linear mixed model analysis. In total, 40 patients reached the HF end point. Multivariable cox regression analysis showed that age (HR 1.04(1.01 to 1.06), p = 0.016), New York Heart Association class (HR 2.30(1.07 to 4.95), p = 0.033), GLS (HR 1.15(1.05 to 1.22), p = 0.001), and left atrial volume (LAVI, HR 2.22(1.10 to 4.50), p = 0.027) were independently associated with the HF end point. Echocardiographic parameters, including GLS and LAVI, remained stable over time in patients without HF end point, but changed significantly in patients who developed HF (group-time interaction, p = 0.042 for GLS and p = 0.027 for LAVI). In conclusion, LV dysfunction is a progressive phenomenon in nonobstructive HC patients which can be detected by repeated echocardiography. Importantly, GLS and LAVI at baseline as well as their changes over time are associated with HF., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Individualized estimation of prognosis after cardiac resynchronization therapy (CRT) remains challenging. Our aim was to develop a multiparametric prognostic risk score (CRT-SCORE) that could be used for patient-specific clinical shared decision making about CRT implantation. The CRT-SCORE was derived from an ongoing CRT registry, including 1,053 consecutive patients (age 67 ± 10 years, 76% male). Using preimplantation variables, 100 multiple imputed datasets were generated for model calibration. Based on multivariate Cox regression models, cross-validated linear prognostic scores were calculated, as well as survival fractions at 1 and 5 years. Specifically, the CRT-SCORE was calculated using atrioventricular junction ablation, age, gender, etiology, New York Heart Association class, diabetes, hemoglobin level, renal function, left bundle branch block, QRS duration, atrial fibrillation, left ventricular systolic and diastolic functions, and mitral regurgitation, and showed a good discriminative ability (areas under the curve 0.773 at 1 year and 0.748 at 5 years). During the long-term follow-up (median 60 months, interquartile range 31 to 85), all-cause mortality was observed in 494 (47%) patients. Based on the distribution of the CRT-SCORE, lower- and higher-risk patient groups were identified. Estimated mean survival rates of 98% at 1 year and 92% at 5 years were observed in the lowest 5% risk group (L5 CRT-SCORE: -4.42 to -1.60), whereas the highest 5% risk group (H5 CRT-SCORE: 1.44 to 2.89) showed poor survival rates: 78% at 1 year and 22% at 5 years. In conclusion, the CRT-SCORE allows accurate prediction of 1- and 5-year survival rates after CRT using readily available and CRT-specific clinical, electrocardiographic, and echocardiographic parameters. The model may assist clinicians in counseling patients and in decision making., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Myocardial scar is known to be associated with limited left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). However, the impact of diffuse myocardial interstitial fibrosis, as assessed with myocardial T 1 mapping cardiac magnetic resonance (CMR), has not been studied in patients with CRT. Therefore, we aimed at evaluating the association between diffuse myocardial interstitial fibrosis, in nonischemic cardiomyopathy patients, and LV reverse remodeling after CRT. A total of 40 patients (61 ± 11 years) with nonischemic cardiomyopathy who underwent CMR before CRT implantation were included. Myocardial T 1 mapping was performed using an inversion-recovery Look-Locker sequence after gadolinium injection. Myocardial contrast-enhanced T 1 time values were assessed from segments without delayed contrast enhancement and normalized for heart rate. At 6-month follow-up, LV reverse remodeling was assessed by the reduction in LV end-systolic volume. Before CRT implantation, mean myocardial contrast-enhanced T 1 time was 351 ± 46 ms. At 6-month follow-up, LV end-systolic volume decreased by 24 ± 21%. Myocardial contrast-enhanced T 1 time showed a significant correlation with LV reverse remodeling (r = 0.5, p = 0.001) together with hemoglobin level, renal function, LV dyssynchrony, and presence of delayed contrast enhancement. Multivariate regression analysis identified myocardial contrast-enhanced T 1 time (β -0.160, p = 0.022), LV dyssynchrony (β -0.267, p = 0.002), and renal function (β -0.334, p = 0.021) as independent associates of LV reverse remodeling. In conclusion, in nonischemic cardiomyopathy, diffuse interstitial myocardial fibrosis quantified with T 1 mapping CMR is independently associated with LV reverse remodeling after CRT and might, therefore, be used to optimize patient selection., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function., Methods: A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all-cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed., Results: Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was -24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88-0.98; P < .01), tricuspid annular plane systolic excursion (hazard ratio, 0.80; 95% confidence interval, 0.66-0.96; P = .02), and right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26; P < .01) were independently associated with 30-day mortality, after adjusting for left ventricular ejection fraction and aortic crossclamping time. Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was independently associated with increased 30-day mortality (hazard ratio, 2.83; 95% confidence interval, 1.64-4.87, P < .01 per additional impaired parameter)., Conclusions: Baseline right ventricular systolic dysfunction is independently associated with increased mortality in patients with ischemic heart failure undergoing surgical left ventricular restoration., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Vasoplegia has been described as a complication after cardiac surgery, particularly in patients with a poor left ventricular ejection fraction. The aim of this study was to assess the incidence, survival and predictors of vasoplegia in patients undergoing heart failure surgery and to propose a risk model., Methods: A retrospective study including heart failure patients who underwent surgical left ventricular restoration, CorCap implantation or left ventricular assist device implantation between 2006 and 2015. Patients were classified by the presence or absence of vasoplegia., Results: Two hundred and twenty-five patients were included. The incidence of vasoplegia was 29%. The 90-day survival rate in vasoplegic patients was lower compared with non-vasoplegic patients (71% vs 91%, P  <   0.001). After adjusting for age, sex and surgical procedure, anaemia (OR 2.195; 95% CI 1.146, 4.204; P  =   0.018) and a higher thyroxine level (OR 1.140; 95% CI 1.033, 1.259; P  =   0.009) increased the risk of vasoplegia; a higher creatinine clearance (OR 0.980; 95% CI 0.965, 0.994; P  =   0.006) and beta-blocker use (OR 0.257; 95% CI 0.112, 0.589; P  =   0.001) decreased the risk. The risk model consisted of the same variables and could adequately identify patients at risk for vasoplegia., Conclusions: Vasoplegia after heart failure surgery is common and results in a lower survival rate. Anaemia and a higher thyroxine level are associated with an increased risk on vasoplegia. In contrast, a higher creatinine clearance and beta-blocker use decrease the risk on vasoplegia. These factors are used in the risk model that may guide treatment strategy., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Myocardial strain analysis by speckle-tracking echocardiography, which can detect subtle abnormalities in left atrial (LA) function, may offer unique insights into LA pathophysiology in patients with cryptogenic stroke (CS). The aim of this study was to investigate whether LA reservoir strain by speckle-tracking echocardiography, as a measure of LA compliance, is impaired in patients with CS and no history of atrial fibrillation., Methods: A retrospective case-control study of 742 patients (mean age, 59 ± 13 years; 54% men; 371 with CS and 371 control subjects) was conducted. LA reservoir strain was quantified using speckle-tracking echocardiography., Results: LA strain was significantly lower among patients with CS than control subjects (30 ± 7.3% vs 34 ± 6.7%, P < .001). Current smoking (odds ratio [OR], 2.6; 95% CI, 1.7-4.0; P < .001), systolic blood pressure (OR, 1.17 per 10 mm Hg increase; 95% CI, 1.06-1.29; P = .001), antihypertensive treatment (OR, 0.45; 95% CI, 0.30-0.66; P < .001), larger indexed left ventricular end-systolic volume (OR, 1.04; 95% CI, 1.01-1.07; P = .02), higher E/E' ratio (OR, 1.06; 95% CI, 1.01-1.11; P = .01), mitral regurgitation (OR, 1.8; 95% CI, 1.2-2.7; P = .003), and lower LA reservoir strain (OR, 1.07 per 1% reduction; 95% CI, 1.05-1.10; P < .001) were independently associated with CS. Importantly, LA reservoir strain conferred incremental discriminatory value in the identification of patients with CS (likelihood ratio P < .001)., Conclusions: Subtle LA dysfunction, as assessed by LA reservoir strain with speckle-tracking echocardiography, is associated with CS independent of other cardiovascular risk factors. These findings suggest a potential role for LA strain to risk-stratify patients in the prevention of stroke., (Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: Implantable cardioverter-defibrillator (ICD) treatment is beneficial in selected patients. However, it remains difficult to accurately predict which patients benefit most from ICD implantation. For this purpose, different risk models have been developed. The aim was to validate and compare the FADES, MADIT, and SHFM-D models., Methods and Results: All patients receiving a prophylactic ICD at the Leiden University Medical Center were evaluated. Individual model performance was evaluated by C-statistics. Model performances were compared using net reclassification improvement (NRI) and integrated differentiation improvement (IDI). The primary endpoint was non-benefit of ICD treatment, defined as mortality without prior ventricular arrhythmias requiring ICD intervention. A total of 1969 patients were included (age 63 ± 11 years; 79% male). During a median follow-up of 4.5 ± 3.9 years, 318 (16%) patients died without prior ICD intervention. All three risk models were predictive for event-free mortality (all: P < 0.001). The C-statistics were 0.66, 0.69, and 0.75, respectively, for FADES, MADIT, and SHFM-D (all: P < 0.001). Application of the SHFM-D resulted in an improved IDI of 4% and NRI of 26% compared with MADIT; IDI improved 11% with the use of SHFM-D instead of FADES (all: P < 0.001), but NRI remained unchanged (P = 0.71). Patients in the highest-risk category of the MADIT and SHFM-D models had 1.7 times higher risk to experience ICD non-benefit than receive appropriate ICD interventions [MADIT: mean difference (MD) 20% (95% CI: 7-33%), P = 0.001; SHFM-D: MD 16% (95% CI: 5-27%), P = 0.005]. Patients in the highest-risk category of FADES were as likely to experience ICD intervention as ICD non-benefit [MD 3% (95% CI: -8 to 14%), P = 0.60]., Conclusion: The predictive and discriminatory value of SHFM-D to predict non-benefit of ICD treatment is superior to FADES and MADIT in patients receiving prophylactic ICD treatment., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.)

Super-response to cardiac resynchronization therapy (CRT) is associated with significant left ventricular (LV) reverse remodeling and improved clinical outcome. The study aimed to: (1) evaluate whether LV reverse remodeling remains sustained during long-term follow-up in super-responders and (2) analyze the association between the course of LV reverse remodeling and ventricular arrhythmias. Of all, primary prevention super-responders to CRT were selected. Super-response was defined as LV end-systolic volume reduction of ≥30% 6 months after device implantation. Cox regression analysis was performed to investigate the association of LV ejection fraction (LVEF) as time-dependent variable with implantable-cardioverter defibrillator (ICD) therapy and mortality. A total of 171 super-responders to CRT-defibrillator were included (mean age 67 ± 9 years; 66% men; 37% ischemic heart disease). Here of 129 patients received at least 1 echocardiographic evaluation after a median follow-up of 62 months (25th to 75th percentile, 38 to 87). LV end-diastolic volume, LV end-systolic volume, and LVEF after 6-month follow-up were comparable with those after 62-month follow-up (p = 0.90, p = 0.37, and p = 0.55, respectively). Changes in LVEF during follow-up in super-responders were independently associated with appropriate ICD therapy (hazard ratio 0.94, 95% CI 0.90 to 0.98; p = 0.005) and all-cause mortality (hazard ratio 0.95, 95% CI 0.91 to 1.00; p = 0.04). A 5% increase in LVEF was associated with a 1.37 times lower risk of appropriate ICD therapy and a 1.30 times lower risk of mortality. In conclusion, LV reverse remodeling in super-responders to CRT remains sustained during long-term follow-up. Changes in LVEF during follow-up were associated with mortality and ICD therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The Seattle Heart Failure Model (SHFM) provides accurate estimates of survival in heart failure (HF) patients. The model is, however, not developed for HF patients with cardiac resynchronization therapy (CRT). The aim of this study was to assess the prognostic value of SHFM combined with QRS morphology and CRT-related change in QRS duration in implantable cardioverter defibrillator (ICD) and CRT defibrillator (CRT-D) recipients., Methods: All patients who underwent prophylactic ICD implantation at the Leiden University Medical Center since 1996 were included. Baseline SHFM, QRS morphology, and duration before and after device implantation were determined. The regression coefficients of the QRS characteristics derived from a Cox regression analysis were implemented in the SHFM. SHFM-estimated survival was compared with Kaplan-Meier observed survival., Results: The current study includes 1,834 defibrillator recipients (63 ± 11 years; 79% male; 53% CRT-D). In 585 (60%) CRT-D recipients a left bundle branch block was present, the mean QRS duration was 147 ± 31 ms before and 151 ± 27 ms after device implantation. After a median follow-up of 4.4 years (25(th) -75(th) percentile 2.7-6.4 years), 285 (29%) CRT-D recipients had died. CRT-related decrease in QRS duration adjusted for QRS morphology was associated with improved survival (hazard ratio 1.05/10 ms; 95% confidence interval [CI]: 1.01-1.09; P = 0.02). The estimated 5-year survival of CRT-D recipients after implementation of the QRS characteristic was 70%, and comparable with the observed 5-year survival of 68% (95% CI: 65-72)., Conclusion: Implementation of native QRS morphology and change in QRS duration due to CRT in the SHFM improves the prognostic value of this model in HF patients with CRT-D., (©2016 Wiley Periodicals, Inc.)

Background and Objectives: Cardiac resynchronization therapy (CRT) is a well established heart failure treatment that has shown to improve renal function. However, landmark CRT trials excluded patients with severe renal dysfunction. Therefore, this study evaluated the effect of CRT on renal function and long-term prognosis in patients with stage 4 CKD., Design, Setting, Participants, & Measurements: This study evaluated 73 consecutive CRT patients (71±10 years) with stage 4 CKD who underwent echocardiographic and renal function evaluation at baseline and 6-month follow-up between 2000 and 2012. As a control group, 18 patients with stage 4 CKD who received an implantable cardioverter defibrillator (ICD) were selected. CRT recipients with ≥15% reduction in left ventricular end-systolic volume at 6-month follow-up were classified as CRT responders. During long-term follow-up (median, 33 months), appropriate defibrillator therapy, heart failure hospitalizations, and all-cause mortality (combined end point) were recorded., Results: At 6-month follow-up, a significant reduction in left ventricular end-systolic volume was observed in CRT patients compared with patients with ICD (from 159±78 to 145±78 ml in CRT patients and from 126±54 to 119±49 ml in ICD patients; P=0.05), and CRT response was observed in 22 patients (30%). Compared with ICD patients, eGFR improved among CRT patients (from 25±4 to 30±9 ml/min per 1.73 m(2); interaction time and group, P=0.04) and was more pronounced among CRT responders (25±3 to 34±9 ml/min per 1.73 m(2); P<0.001). The combined end point was observed in 17 ICD and 62 CRT patients. CRT patients showed superior survival compared with ICD patients (log-rank P=0.03). More importantly, CRT response was independently associated with improved survival free from the combined end point (hazard ratio, 0.51; 95% confidence interval, 0.27 to 0.98; P=0.04) after adjustment for clinical and echocardiographic parameters., Conclusions: Response to CRT occurs in approximately 30% of patients with stage 4 CKD, which is less than in the average CRT population. CRT was associated with better clinical outcome, and particularly, CRT response was associated with improvement in eGFR and better long-term prognosis., (Copyright © 2015 by the American Society of Nephrology.)

Aims: Mortality and ventricular arrhythmias are reduced in patients responding to cardiac resynchronization therapy (CRT). This response is accompanied by improvement in LVEF, and some patients even outgrow original eligibility criteria for implantable cardioverter-defibrillator (ICD) implantation. It is however unclear if these patients still benefit from ICD treatment. The current study aimed to evaluate if the incidence of ICD therapy is related to the extent of CRT response., Methods and Results: All patients who underwent primary prevention CRT-defibrillator implantation were included. They were divided into subgroups according to the reduction in LV end-systolic volume (LVESV) 6 months after implantation. Pre-defined subgroups were: negative responders (increased LVESV), non-responders (decreased LVESV 0-14%), responders (decreased LVESV 15-29%), and super-responders (decreased LVESV ≥30%). During a median follow-up of 57 months (25th-75th percentile 39-84), 512 patients were studied [101 (20%) negative responders, 101 (20%) non-responders, 149 (29%) responders, and 161 (31%) super-responders]. In the first year of follow-up super-responders received significantly less appropriate ICD therapy (3% vs. 12%; P < 0.001). The 5-year cumulative incidence of appropriate ICD therapy was 31% [95% confidence interval (CI) 19-43] in negative responders, 39% (95% CI 25-53) in non-responders, 34% (95% CI 25-43) in responders, and 27% (95% CI 18-35) in super-responders, respectively (p = 0.13)., Conclusions: The extent of CRT response was associated with a parallel reduction of appropriate device therapy during the first year of follow-up. Thereafter, no association was observed. Furthermore, 23% of super-responders were treated for potentially life-threatening arrhythmias and benefit from ICD treatment., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

Background: Right ventricular apical (RVA) pacing may induce left ventricular (LV) dyssynchrony. The long-term prognostic implications of induction of LV dyssynchrony were retrospectively evaluated in a cohort of patients who underwent RVA pacing., Methods: A total of 169 patients (62 ± 13 years, 69% male) with high RVA pacing burden were included. Echocardiographic evaluation of LV volumes, ejection fraction, and dyssynchrony were performed before and after device implantation. LV dyssynchrony was assessed by 2-dimensional radial strain speckle tracking echocardiography. Based on the median LV dyssynchrony value after RVA pacing, the patient population was dichotomized (induced and noninduced LV dyssynchrony groups) and was followed up for the occurrence of all-cause mortality and heart failure (HF) hospitalization., Results: Baseline mean LV ejection fraction was 51 ± 11%. Median LV dyssynchrony value was 40 ms (12-85 ms) before RVA pacing and increased to 91 ms (81-138 ms) after a median of 13 months (3-26 months) after RVA pacing. Median follow-up duration was 70 months (interquartile range 42-96 months). Patients with induced LV dyssynchrony, defined as LV dyssynchrony value superior to the median at follow-up (≥91 ms), showed higher mortality rates (5% and 27% vs. 1% and 3% at 3 and 5 years follow-up; log-rank P = 0.003) and HF hospitalization rates (18% and 24% vs. 3% and 4% at 3 and 5 years follow-up; log-rank P < 0.001) than patients with LV dyssynchrony <91 ms after RVA pacing. A multivariate model was developed to identify independent associates of a combined endpoint of all-cause mortality or HF hospitalization. Induction of LV dyssynchrony was independently associated with increased risk of combined endpoint (HR [95% CI]: 3.369 [1.732-6.553], P < 0.001)., Conclusion: Induction of LV dyssynchrony by RVA pacing is associated with worse long-term mortality and increased HF hospitalization rates., (© 2014 Wiley Periodicals, Inc.)

Cardiac resynchronization therapy (CRT) induces left ventricular (LV) reverse remodeling by synchronizing LV mechanical activation. We evaluated changes in segmental LV activation after CRT and related them to CRT response. A total of 292 patients with heart failure (65 ± 10 years, 77% men) treated with CRT underwent baseline echocardiographic assessment of LV volumes and ejection fraction. Time-to-peak radial strain was measured for 6 midventricular LV segments with speckle-tracking strain imaging. Moreover, the time difference between the peak radial strain of the anteroseptal and the posterior segments was calculated to obtain LV dyssynchrony. After 6 months, LV volumes, segmental LV mechanical activation timings, and LV dyssynchrony were reassessed. Response to CRT was defined as ≥15% decrease in LV end-systolic volume at 6-month follow-up. Responders (n = 177) showed LV resynchronization 6 months after CRT (LV dyssynchrony from 200 ± 127 to 85 ± 86 ms; p <0.001) by earlier activation of the posterior segment (from 438 ± 141 to 394 ± 132 ms; p = 0.001) and delayed activation of the anteroseptal segment (from 295 ± 155 to 407 ± 138 ms; p <0.001). In contrast, nonresponders (n = 115) experienced an increase in LV dyssynchrony 6 months after CRT (from 106 ± 86 to 155 ± 112 ms; p = 0.001) with an earlier activation of posterior wall (from 391 ± 139 to 355 ± 136 ms; p = 0.039) that did not match the delayed anteroseptal activation (from 360 ± 148 to 415 ± 122 ms; p = 0.001). In conclusion, responders to CRT showed LV resynchronization through balanced lateral and anteroseptal activations. In nonresponders, LV dyssynchrony remains, by posterior wall preactivation and noncompensatory delayed septal wall activation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Although randomized trials have shown the beneficial effect on survival of an implantable cardioverter defibrillator (ICD) as primary prevention therapy in selected patients, data concerning the cost-effectiveness in routine clinical practice remain scarce. Accordingly, the purpose of this study was to assess the cost-effectiveness of primary prevention ICD implantation in the real world., Methods: Patients receiving primary prevention single-chamber or dual-chamber ICD implantation at the Leiden University Medical Center were included in the study. Using a Markov model, lifetime cost, life years (LYs), and gained quality-adjusted life years (QALYs) were estimated for device recipients and control patients. Data on mortality, complication rates, and device longevity were retrieved from our center and entered into the Markov model. To account for model assumptions, one-way deterministic and probabilistic sensitivity analyses were performed. Importantly, calculations for the estimated incremental cost-effectiveness rate (ICER) per QALY gained are based on several numbers of assumptions, and accordingly findings may have over- or underestimated the cost-effectiveness of ICD therapy., Results: Primary prevention ICD implantation adds an estimated mean of 2.07 LYs and 1.73 QALYs. Increased lifetime cost for single-chamber and dual-chamber ICD recipients were estimated at €60,788 and €64,216, respectively. This resulted for single-chamber ICD recipients, in an estimated ICER of €35,154 per QALY gained. In dual-chamber ICD recipients, an estimated ICER of €37,111 per QALY gained was calculated. According to the probabilistic sensitivity analysis, estimated cost per QALY gained are €35,837 (95% confidence interval [CI]: €28,368-€44,460) for single-chamber and €37,756 (95% CI: €29,055-€46,050) for dual-chamber ICDs., Conclusions: On the basis of data and detailed costs, derived from routine clinical practice, ICD therapy in selected patients with a reduced left ventricular ejection fraction appears to be cost-effective., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Background: The relationship between changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiographic or clinical definitions of response to cardiac resynchronization therapy (CRT) has not been evaluated. The aims of the present evaluation were to assess: (1) the relationship between changes in NT-proBNP after 6 months of CRT and clinical and echocardiographic responses; (2) the association between NT-proBNP changes and long-term outcome., Methods: In 170 patients treated with CRT (age 61 ± 11 years, 75% male), clinical and echocardiographic parameters and circulating NT-proBNP levels were assessed at baseline and 6 months after CRT. At 6 months follow-up, improvement in New York Heart Association class ≥ 1 point, decrease in left ventricular end-systolic volume ≥ 15%, and decrease in NT-proBNP ≥ 15% defined clinical, echocardiographic, and neurohormonal CRT response, respectively. All-cause mortality data were collected and related to neurohormonal response., Results: Neurohormonal, echocardiographic, and clinical response rates were 54%, 58%, and 66%, respectively. The majority of patients (71%) showing echocardiographic response had NT-proBNP reduction ≥ 15%. In contrast, only 58% of patients who showed clinical response also had NT-proBNP reduction ≥ 15%. During a median follow-up of 32 months, 40 patients died. Patients with neurohormonal response demonstrated a superior long-term outcome compared to patients without neurohormonal response (log-rank P = 0.02)., Conclusions: NT-proBNP reduction ≥ 15% showed better agreement with echocardiographic response compared to clinical response. Neurohormonal response was associated with superior long-term outcome compared to insufficient reduction in NT-proBNP levels., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Background: The mechanism of the beneficial effects of exercise training on autonomic derangement and neurohumoral activation in chronic heart failure (CHF) is largely unexplained. In our here-presented hypothesis-generating study we propose that part of these effects is mediated by the exercise-accompanying somatosensory nerve traffic. To demonstrate this, we compared the effects of periodic electrical somatosensory stimulation in patients with CHF with the effects of exercise training and with usual care., Methods: In a randomized controlled study we measured, in CHF patients, changes in blood pressure, baroreflex sensitivity (BRS), neurohormones, exercise capacity and quality of life (QOL) in response to periodic somatosensory stimulation in the form of 2 Hz transcutaneous electrical nerve stimulation (TENS) at both feet, in response to conventional exercise training (EXTR) and, as control (CTRL), in patients with usual care only., Results: Group sizes were N=31 (TENS group), N=25 (EXTR group) and N=30 (CTRL group), respectively. Practically all improvements in BRS, neurohormone concentrations, exercise capacity and QOL in the TENS group were comparable to, or sometimes even better than in the EXTR group. These improvements were not observed in the CTRL group., Conclusions: This study demonstrates that periodic electrical somatosensory stimulation is as effective as exercise training in improving BRS, neurohormone concentrations, exercise capacity and QOL in CHF patients. These results encourage exploration of exercise modalities that concentrate on rhythm rather than on effort, with the purpose to normalize autonomic derangement and neurohumoral activation in CHF., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Aims: Mitral valve repair in patients with functional mitral regurgitation (FMR) has been associated with beneficial left ventricular (LV) reverse remodelling. Recently, galectin-3 emerged as a marker of myocardial inflammation and fibrosis which may influence LV remodelling after surgery. The aim of the current study was to evaluate the association between pre-operative galectin-3 levels and LV reverse remodelling in heart failure patients with significant FMR who underwent mitral valve repair., Methods and Results: In total, 42 heart failure patients (66 ± 10 years, 69% male) were evaluated. Plasma galectin-3 levels were assessed pre-operatively. Two-dimensional echocardiographic parameters were measured at baseline, and at 6 and 12 months after surgery. LV reverse remodelling was defined as a decrease in LV end-systolic volume ≥15% at 6 months follow-up. In total, 57% of the patients showed LV reverse remodelling. Patients with LV reverse remodelling showed significantly lower pre-operative galectin-3 levels (17.5 ± 5.6 vs. 23.7 ± 9.9 ng/mL, P = 0.009) compared with patients without LV reverse remodelling. In addition, patients with galectin-3 ≤18.2 ng/mL had a six-fold higher probability of showing LV reverse remodelling after surgery as compared with patients with levels >18.2 ng/mL (odds ratio 6.58, 95% confidence interval 1.32-33.33, P = 0.02)., Conclusion: High pre-operative plasma galectin-3 is independently associated with the absence of LV reverse remodelling after mitral valve repair. Galectin-3 may be useful to identify heart failure patients who will need additional treatment to obtain beneficial LV reverse remodelling.

Background: Clinical or echocardiographic mid-term responses to cardiac resynchronization therapy (CRT) may have a different influence on a long-term prognosis of heart failure patients treated with CRT. The aim of the evaluation was to establish which definition of response to CRT, clinical or echocardiographic, best predicts long-term prognosis., Methods and Results: A total of 679 heart failure patients treated with CRT were included. All the patients underwent a complete history and physical examination and transthoracic echocardiogram prior to CRT implantation and at 6-month follow-up. The clinical and echocardiographic responses to CRT were defined based on clinical improvement (≥1 NYHA class) and LV reverse remodelling (reduction in LV end-systolic volume ≥15%) at 6-month follow-up, respectively. All the patients were prospectively followed up for the occurrence of death. The mean age was 65 ± 11 years and 79% of the patients were male. At 6-month follow-up, 510 (77%) patients showed clinical response to CRT and 412 (62%) patients showed echocardiographic response to CRT. During a mean follow-up of 37 ± 22 months, 140 (21%) patients died. Clinical and echocardiographic responses to CRT were both significantly related to all-cause mortality on univariable analysis. However, on multivariable Cox-regression analysis only echocardiographic response to CRT was independently associated with superior survival (hazard ratio: 0.38; 95% CI: 0.27-0.50; P < 0.001)., Conclusion: In a large population of heart failure patients treated with CRT, the reduction in LV end-systolic volume at the mid-term follow-up demonstrated to be a better predictor of long-term survival than improvement in the clinical status.

Objectives: Right ventricular (RV) function is an important prognostic marker in heart failure. However, its impact on all-cause mortality following cardiac resynchronisation therapy (CRT) independent of confounding factors has not been evaluated. Furthermore, evidence concerning the effect of CRT on RV function is limited. The study's aims were to: (1) assess the prognostic importance of RV function among CRT recipients, and (2) characterise RV functional change following CRT and its determinants., Design: Retrospective observational study., Setting: Single tertiary centre., Patients: A total of 848 CRT recipients (median age 65 years, 78% male, 60% ischaemic) underwent echocardiography before and 6 months after CRT. RV function was evaluated using tricuspid annular plane systolic excursion (TAPSE), with a ≤14 mm threshold indicating severe RV impairment. The primary endpoint was long-term all-cause mortality., Results: Significant baseline RV dysfunction was observed in 286 (34%) individuals. After a median 44 months, 288 deaths occurred. RV impairment was associated with a greater incidence of all-cause mortality (log-rank p<0.001). Independent predictors of this endpoint were functional class, ischaemic aetiology, diabetes, atrial fibrillation, renal dysfunction, bigger left ventricular (LV) end-systolic volume, less LV dyssynchrony and reduced TAPSE. Importantly, TAPSE added prognostic value to these recognised prognostic parameters (likelihood-ratio test p<0.001). Furthermore, improvement in RV function after CRT was independent of the improvement in LV systolic function but significantly associated with the improvement in LV diastolic function. Importantly, a favourable RV functional response to CRT was associated with superior survival., Conclusions: RV function is an independent predictor of long-term outcome following CRT.

Implantation of a left ventricular assist device can be challenging in patients with an altered apical anatomy after cardiac surgery or as the result of the presence of a calcified apical aneurysm. In this paper we present 2 cases with a challenging apical anatomy and introduce a new surgical technique facilitating left ventricular assist device implantation in these patients., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: One of the major drawbacks of implantable cardioverter-defibrillator (ICD) treatment is the limited device service life. Thus far, data concerning ICD longevity under clinical circumstances are scarce. In this study, the ICD service life was assessed in a large cohort of ICD recipients., Objective: To assess the battery longevity of ICDs under clinical circumstances., Methods: All patients receiving an ICD in the Leiden University Medical Center were included in the analysis. During prospectively recorded follow-up visits, reasons for ICD replacement were assessed and categorized as battery depletion and non-battery depletion. Device longevity and battery longevity were calculated. The impact of device type, generation, manufacturer, the percentage of pacing, the pacing output, and the number of shocks on the battery longevity was assessed., Results: Since 1996, 4673 ICDs were implanted, of which 1479 ICDs (33%) were replaced. Mean device longevity was 5.0 ± 0.1 years. A total of 1072 (72%) ICDs were replaced because of battery depletion. Mean battery longevity of an ICD was 5.5 ± 0.1 years. When divided into different types, mean battery longevity was 5.5 ± 0.2 years for single-chamber ICDs, 5.8 ± 0.1 for dual-chamber ICDs, and 4.7 ± 0.1 years for cardiac resynchronization therapy-defibrillators (P <.001). Devices implanted after 2002 had a significantly better battery longevity as compared with devices implanted before 2002 (5.6 ± 0.1 years vs 4.9 ± 0.2 years; P <.001). In addition, large differences in battery longevity between manufacturers were noted (overall log-rank test, P <.001)., Conclusions: The majority of ICDs were replaced because of battery depletion. Large differences in longevity exist between different ICD types and manufacturers. Modern ICD generations demonstrated improved longevity., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: To evaluate the effects of cardiac resynchronization therapy (CRT) on long-term survival of patients without baseline left ventricular (LV) mechanical dyssynchrony., Methods and Results: A total of 290 heart failure patients (age 67 ± 10 years, 77% males) without significant baseline LV dyssynchrony (<60 ms as assessed with tissue Doppler imaging) were treated with CRT. Patients were divided according to the median LV dyssynchrony measured after 48 h of CRT into two groups. All-cause mortality was compared between the subgroups. In addition, the all-cause mortality rates of these subgroups were compared with the all-cause mortality of 290 heart failure patients treated with CRT who showed significant LV dyssynchrony (≥60 ms) at baseline. In the group of patients without significant LV dyssynchrony, median LV dyssynchrony increased from 22 ms (inter-quartile range 16-34 ms) at baseline to 40 ms (24-56 ms) 48 h after CRT. The cumulative mortality rates at 1-, 2-, and 3-year follow-up of patients with LV dyssynchrony ≥40 ms 48 h after CRT implantation were significantly higher when compared with patients with LV dyssynchrony <40 ms (10, 17, and 23 vs. 3, 8, and 10%, respectively; log-rank P< 0.001). Finally, the cumulative mortality rates at 1-, 2-, and 3-year follow-up of patients with baseline LV dyssynchrony were 3, 8, and 11%, respectively (log-rank P= 0.375 vs. patients with LV dyssynchrony <40 ms). Induction of LV dyssynchrony after CRT was an independent predictor of mortality (hazard ratio: 1.247; P= 0.009)., Conclusion: In patients without significant LV dyssynchrony, the induction of LV dyssynchrony after CRT may be related to a less favourable long-term outcome.

'Multimodality' imaging--the side-by-side interpretation of data obtained from various noninvasive imaging techniques, such as echocardiography, radionuclide techniques, multidetector CT (MDCT), and MRI--allows anatomical, morphological, and functional data to be combined, increases diagnostic accuracy, and improves the efficacy of cardiovascular interventions and clinical outcomes. During the past decade, advances in software and hardware have allowed co-registration of various imaging modalities, resulting in cardiac 'hybrid' or 'fusion' imaging. In this Review, we discuss the roles of both multimodality and hybrid imaging in three broad areas of cardiology--coronary artery disease (CAD), heart failure, and valvular heart disease. In the evaluation of CAD, integration of either single-photon emission computed tomography (SPECT) or PET with CT coronary angiography provides both morphological and functional data in a single procedure. Accordingly, the functional consequences (myocardial hypoperfusion on SPECT or PET) of anatomical pathology (coronary anatomy on MDCT or MRI) can be assessed. Co-registration of PET and MRI data sets to provide cellular and molecular information on plaque composition and stability is now possible. Furthermore, novel imaging modalities have been implemented to guide electrophysiological and transcatheter-based procedures, such as cardiac resynchronization therapy (an established treatment for patients with heart failure), and transcatheter valve repair or replacement procedures.

The risk scores developed for the prediction of an adverse outcome in patients after ST-segment elevation myocardial infarction (STEMI) have mostly addressed patients treated with thrombolysis and evaluated solely all-cause mortality as the primary end point. Primary percutaneous coronary intervention in patients with STEMI has improved the outcome significantly and might have changed the relative contribution of different risk factors. Our patient population included 1,484 consecutive patients admitted with STEMI who had undergone primary percutaneous coronary intervention. The clinical, angiographic, and echocardiographic data obtained during hospitalization were used to derive a risk score for the prediction of short-term (30-day) and long-term (1- and 4-year) cardiovascular mortality and hospitalization for heart failure. During a median follow-up of 30 months, 87 patients (6%) died from cardiovascular mortality or were hospitalized for heart failure. Multivariate Cox regression analyses identified age ≥70 years, Killip class ≥2, diabetes, left anterior descending coronary artery as the culprit vessel, 3-vessel disease, peak cardiac troponin T level ≥3.5 μg/L, left ventricular ejection fraction ≤40%, and heart rate at discharge ≥70 beats/min as relevant factors for the construction of the risk score. The discriminatory power of the model as assessed using the areas under the receiver operating characteristic curves was good (0.84, 0.83, and 0.81 at 30 days and 1 and 4 years, respectively), and the patients could be allocated to low-, intermediate-, or high-risk categories with an event rate of 1%, 6%, and 24%, respectively. In conclusion, the current risk model demonstrates for the first time that 8 parameters readily available during the hospitalization of patients with STEMI treated with primary percutaneous coronary intervention can accurately stratify patients at long-term follow-up (≤4 years after the index infarction) into low-, intermediate-, and high-risk categories., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to evaluate the impact of upgrading implantable cardioverter-defibrillator (ICD) therapy to cardiac resynchronization therapy (CRT) combined with defibrillator (CRT-D) on the occurrence of ventricular arrhythmia (VA) and appropriate ICD therapies., Background: CRT has been shown to improve left ventricular (LV) systolic function and induce reverse LV remodeling. In addition, it has been hypothesized that CRT may reduce the incidence of VA., Methods: Heart failure patients receiving an upgrade from ICD to CRT-D were evaluated. Patients were considered responders to CRT if LV end-systolic volume reduced ≥15% at 6 months of follow-up. Episodes of VA, triggering device therapy (anti-tachycardia pacing and shocks) were recorded before and after upgrade for the overall population. In addition, these outcomes were compared between CRT responders and nonresponders during the follow-up period after CRT response was assessed., Results: One hundred fifteen patients (93 males [81%], age 65 ± 12 years) were evaluated during a mean follow-up of 54 ± 34 months before CRT-D upgrade and 37 ± 27 months after upgrade. In CRT responders (n = 70), the frequency of VA requiring appropriate device therapy demonstrated a trend toward a decrease from 0.51 ± 0.79 to 0.30 ± 0.59 per patient per year after CRT-D upgrade (p = 0.052). In CRT nonresponders (n = 45), the frequency of VA requiring appropriate device therapy significantly increased from 0.40 ± 0.69 to 1.21 ± 2.53 per patient per year after CRT-D upgrade (p = 0.014)., Conclusions: After upgrade from ICD to CRT-D, nonresponders to CRT showed a significant increase in VA burden requiring appropriate device therapy., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiac resynchronization therapy improves clinical symptoms and prognosis of heart failure patients. However, it has been shown that up to 40% of patients do not respond to this therapy. Three main determinants of cardiac resynchronization therapy response have been identified: left ventricular dyssynchrony, left ventricular lead position, and extent and location of myocardial scar tissue. Two-dimensional echocardiography is the first imaging technique to evaluate patients who may be candidates for cardiac resynchronization therapy. However, a multimodality approach based on 3-dimensional imaging techniques may provide a more comprehensive evaluation of these patients by combining the assessment of the aforementioned pathophysiological determinants of cardiac resynchronization therapy response., (Copyright © 2011 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Background: One of the beneficial effects of exercise training in chronic heart failure (CHF) is an improvement in baroreflex sensitivity (BRS), a prognostic index in CHF. In our hypothesis-generating study we propose that at least part of this effect is mediated by neural afferent information, and more specifically, by exercise-induced somatosensory nerve traffic., Objective: To compare the effects of periodic electrical somatosensory stimulation on BRS in patients with CHF with the effects of exercise training and with usual care., Methods: We compared in stable CHF patients the effect of transcutaneous electrical nerve stimulation (TENS, N = 23, LVEF 30 ± 9%) with the effects of bicycle exercise training (EXTR, N = 20, LVEF 32 ± 7%). To mimic exercise-associated somatosensory ergoreceptor stimulation, we applied periodic (2/s, marching pace) burst TENS to both feet. TENS and EXTR sessions were held during two successive days., Results: BRS, measured prior to the first intervention session and one day after the second intervention session, increased by 28% from 3.07 ± 2.06 to 4.24 ± 2.61 ms/mmHg in the TENS group, but did not change in the EXTR group (baseline: 3.37 ± 2.53 ms/mmHg; effect: 3.26 ± 2.54 ms/mmHg) (P(TENS vs EXTR) = 0.02). Heart rate and systolic blood pressure did not change in either group., Conclusions: We demonstrated that periodic somatosensory input alone is sufficient and efficient in increasing BRS in CHF patients. This concept constitutes a basis for studies towards more effective exercise training regimens in the diseased/impaired, in whom training aimed at BRS improvement should possibly focus more on the somatosensory aspect., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Aims: Changes in left ventricular (LV) diastolic function after cardiac resynchronization therapy (CRT) in relation to LV reverse remodelling and heart failure aetiology have not been extensively characterized. The aims of the study were to evaluate changes in LV diastolic function with speckle-tracking echocardiography in relation to: (i) cardiac resynchronization therapy response (LV remodelling) and (ii) heart failure aetiology., Methods and Results: A total of 192 heart failure patients undergoing CRT implantation were evaluated. Speckle-tracking echocardiography was performed before and 6 months after implantation and reliable analysis was obtained in 188 patients. Left ventricular diastolic function was assessed by measuring diastolic strain rate during the isovolumic relaxation period (SR(IVR)) and by calculating the ratio of peak transmitral E-wave to SR(IVR) (E/SR(IVR)). Changes in LV diastolic parameters were evaluated in responders and non-responders and in patients with ischaemic and non-ischaemic cardiomyopathy. Response to CRT was defined as ≥15% reduction in LV end-systolic volume at 6 months follow-up. One-hundred and nine patients (58%) were defined as responders. Significant improvements in LV diastolic performance were observed in responders with improvement in SR(IVR) (from 0.14 ± 0.08 to 0.18 ± 0.12 s(-1), P= 0.001) and E/SR(IVR) (from 834 ± 840 to 641 ± 612, P= 0.04). In addition, LV relaxation improved in patients with non-ischaemic aetiology (SR(IVR): from 0.15 ± 0.08 to 0.19 ± 0.13 s(-1), P= 0.004). In contrast, LV relaxation did not improve in non-responders and in patients with ischaemic heart disease., Conclusions: Novel diastolic strain rate indices are useful for evaluating changes in LV diastolic function after CRT. Improvement in diastolic function was only observed in responders to CRT and patients with non-ischaemic aetiology.

The number of patients with congenital heart disease (CHD) has significantly increased over the last decades. The CHD population has a high prevalence of heart failure during late follow-up and this is a major cause of mortality. Cardiac resynchronization therapy (CRT) may be a promising therapy to improve the clinical outcome of CHD and paediatric patients with heart failure. However, the CHD and paediatric population is a highly heterogeneous group with different anatomical substrates that may influence the effects of CRT. Echocardiography is the mainstay imaging modality to evaluate CHD and paediatric patients with heart failure and novel echocardiographic tools permit a comprehensive assessment of cardiac dyssynchrony that may help selecting candidates for CRT. This article reviews the role of CRT in the CHD and paediatric population with heart failure. The current inclusion criteria for CRT as well as the outcomes of different anatomical subgroups are evaluated. Finally, echocardiographic assessment of mechanical dyssynchrony in the CHD and paediatric population and its role in predicting response to CRT is comprehensively discussed.

Cardiac resynchronization therapy (CRT) is an established treatment of patients with heart failure. Several baseline characteristics can influence the CRT outcomes, and little is known about the effect of gender. The aim of the present study was to elucidate the gender-related differences in long-term survival after CRT. A total of 578 consecutive patients with heart failure underwent CRT. At baseline and 6 months after CRT, the clinical and echocardiographic parameters were obtained. All-cause mortality was compared between the men and women. The study population included 431 men (67 ± 9 years) and 147 women (65 ± 11 years). No differences in the clinical and echocardiographic characteristics were observed between the men and women, except for left bundle branch block and a nonischemic etiology of heart failure, which were more frequent in women (81% vs 68% and 63% vs 33%, respectively; p <0.01), and atrial fibrillation, which was more prevalent in men (20% vs 10%, respectively; p = 0.01). During a mean follow-up of 34 ± 25 months, 197 patients died (158 men and 39 women). Kaplan-Meier analysis showed a significant difference in long-term survival between the women and men (p = 0.007). The 2-year all-cause mortality rate was 15% in men and 8% in women (p = 0.025). Cox proportional hazard analysis revealed female gender is an independent predictor of long-term survival, together with heart failure etiology and renal function. In particular, women with heart failure due to a nonischemic etiology showed the best long-term survival rate. In conclusion, female gender and nonischemic etiology were independently associated with better long-term survival after CRT., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Cardiac resynchronization therapy (CRT) has emerged as a treatment option for patients with end-stage heart failure and a QRS duration ≥120 ms. Nonetheless, many patients with a prolonged QRS do not demonstrate left ventricular (LV) mechanical dyssynchrony, and discrepancies between electrical and mechanical dyssynchrony have been observed. In addition, several studies demonstrated that superior benefits after CRT could be achieved when the LV pacing lead was positioned at the most delayed myocardial segment., Methods: A total of 248 heart failure patients scheduled for CRT were included. In all patients, a 12-lead electrocardiogram and 2-dimensional echocardiogram were obtained. Patients were divided into 5 QRS configuration subgroups: narrow, left bundle-branch block, right bundle-branch block, intraventricular conduction delay, and right ventricular pacing. With speckle-tracking radial strain analysis, we evaluated time to peak radial strain. Next, the segments with the least and with the most mechanical activation delay were identified, and LV dyssynchrony was defined as the time delay between the two., Results: Mean QRS duration was 164 ± 31 ms. Mean LV dyssynchrony in all patients was 186 ± 122 ms. Site of latest activation was predominantly located in the lateral (27%), posterior (26%), and inferior (20%) segments. Furthermore, extent of LV dyssynchrony was comparable between QRS configuration subgroups. An unequal distribution of LV segments with the most mechanical delay was observed in the left bundle-branch block and right ventricular pacing subgroups (P < .001 for both), whereas in the narrow, right bundle-branch block, and intraventricular conduction delay subgroups, a more homogeneous distribution was noted. No differences in distribution pattern or in extent of LV dyssynchrony were observed between ischemic and nonischemic heart failure patients., Conclusion: The lateral, posterior, and inferior segments take up 73% of the total latest activated segments in heart failure patients eligible for CRT. Presence of LV dyssynchrony can be observed in all QRS configurations. The site of latest activation may be outside the lateral or posterior segment, making echocardiographic assessment of LV dyssynchrony and site of latest activation a valuable technique to optimize patient outcome after CRT., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Lack of response to cardiac resynchronization therapy (CRT) ranges between 30% to 40% of heart failure (HF) patients. The present study aimed to evaluate the clinical and echocardiographic determinants of nonresponse to CRT., Methods: A total of 581 patients (66.4 ± 10.0 years, 77.9% male) with advanced HF scheduled for CRT implantation were included. Clinical and echocardiographic evaluations were performed at baseline and 6 months of follow-up. Nonresponse was defined as no improvement in the New York Heart Association functional class, death from worsening HF or heart transplantation, and <15% reduction in left ventricular (LV) end-systolic volume., Results: At 6 months of follow-up, 254 patients (44%) did not respond to CRT. The nonresponders were more frequently male (81.9% vs 74.3%, P = .030) and had ischemic cardiomyopathy (69.7% vs 53.2%, P < .001), shorter QRS duration (150.6 ± 29.9 milliseconds vs 156.0 ± 32.5 milliseconds, P = .041), worse New York Heart Association functional class (2.8 ± 0.6 vs 2.7 ± 0.6, P = .008) and shorter 6-minute walk distance (297.9 ± 110.7 m vs 331.8 ± 112.6 m, P = .001), larger left atrial volumes (44.9 ± 16.9 mL/m(2) vs 40.9 ± 17.6 mL/m(2), P = .006), less baseline LV dyssynchrony (56.2 ± 41.3 milliseconds vs 69.1 ± 39.9 milliseconds, P < .001), and, more frequently, anterior LV lead position (12.4% vs 4.0%, P = .007). At multivariate analysis, only the ischemic etiology of HF (odds ratio [OR] 2.264, P = .005), shorter 6-minute walk distance at baseline (OR 0.998, P = .030), less baseline LV dyssynchrony (OR 0.989, P < .001), and anterior LV lead position (OR 3.713, P < .010) remained independent predictors of nonresponse to CRT., Conclusions: Ischemic etiology of HF, shorter baseline 6-minute walk distance, less baseline LV dyssynchrony, and anterior LV lead position are independent determinants of nonresponse to CRT., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: The relative merits of left ventricular (LV) dyssynchrony, LV lead position, and myocardial scar to predict long-term outcome after cardiac resynchronization therapy remain unknown and were evaluated in the present study., Methods and Results: In 397 ischemic heart failure patients, 2-dimensional speckle tracking imaging was performed, with comprehensive assessment of LV radial dyssynchrony, identification of the segment with latest mechanical activation, and detection of myocardial scar in the segment where the LV lead was positioned. For LV dyssynchrony, a cutoff value of 130 milliseconds was used. Segments with <16.5% radial strain in the region of the LV pacing lead were considered to have extensive myocardial scar (>50% transmurality, validated in a subgroup with contrast-enhanced magnetic resonance imaging). The LV lead position was derived from chest x-ray. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. Mean baseline LV radial dyssynchrony was 133±98 milliseconds. In 271 patients (68%), the LV lead was placed at the latest activated segment (concordant LV lead position), and the mean value of peak radial strain at the targeted segment was 18.9±12.6%. Larger LV radial dyssynchrony at baseline was an independent predictor of superior long-term survival (hazard ratio, 0.995; P=0.001), whereas a discordant LV lead position (hazard ratio, 2.086; P=0.001) and myocardial scar in the segment targeted by the LV lead (hazard ratio, 2.913; P<0.001) were independent predictors of worse outcome. Addition of these 3 parameters yielded incremental prognostic value over the combination of clinical parameters., Conclusions: Baseline LV radial dyssynchrony, discordant LV lead position, and myocardial scar in the region of the LV pacing lead were independent determinants of long-term prognosis in ischemic heart failure patients treated with cardiac resynchronization therapy. Larger baseline LV dyssynchrony predicted superior long-term survival, whereas discordant LV lead position and myocardial scar predicted worse outcome.

Background: Restrictive mitral annuloplasty (RMA) is increasingly applied to treat functional mitral regurgitation in heart failure patients. Previous studies indicated beneficial clinical effects with low recurrence rates. However, the underlying pathophysiology is complex and outcome in terms of left ventricular function is not well known. We investigated chronic effects of RMA on ventricular function in relation to clinical outcome., Methods: Heart failure patients (n = 11) with severe mitral regurgitation scheduled for RMA were analyzed at baseline (presurgery) and midterm follow-up by invasive pressure-volume loops, using conductance catheters. Clinical performance was evaluated by New York Heart Association class, quality-of-life-score, and 6-minute hall-walk-test., Results: All patients were alive without recurrence of mitral regurgitation at follow-up (9.4 ± 4.1 months). Clinical parameters improved significantly (all p < 0.05). Global cardiac function, assessed by cardiac output, stroke volume, and stroke work did not change after RMA. Reverse remodeling was demonstrated by decreased end-systolic and end-diastolic volumes (16% and 11%, both p < 0.001). Systolic function improved, evidenced by increased ejection fraction (0.32 ± 0.05 to 0.36 ± 0.07, p = 0.001) and leftward shift of the end-systolic pressure-volume relation (ESV(100): 116 ± 43 to 74 ± 26 mL, p < 0.001). Diastolic function, however, demonstrated impairment by increased tau (69 ± 13 to 80 ± 14 ms, p < 0.001) and stiffness constant (0.022 ± 0.022 to 0.031 ± 0.028 mL(-1), p = 0.001)., Conclusions: Restrictive mitral annuloplasty significantly improved clinical status without recurrence of mitral regurgitation at midterm follow-up in patients with heart failure. Hemodynamic analyses demonstrated significant reverse remodeling with unchanged global function and improved systolic function, but some signs of diastolic impairment. Overall, RMA appears an appropriate therapy for patients with dilated cardiomyopathy and functional mitral regurgitation., (Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Aims: current criteria for cardiac resynchronization therapy (CRT) are restricted to patients with a wide QRS complex (>120 ms). Overall, only 30% of heart failure patients demonstrate a wide QRS complex, leaving the majority of heart failure patients without this treatment option. However, patients with a narrow QRS complex exhibit left ventricular (LV) mechanical dyssynchrony, as assessed with echocardiography. To further elucidate the possible beneficial effect of CRT in heart failure patients with a narrow QRS complex, this two-centre, non-randomized observational study focused on different echocardiographic parameters of LV mechanical dyssynchrony reflecting atrioventricular, interventricular and intraventricular dyssynchrony, and the response to CRT in these patients., Methods and Results: a total of 123 consecutive heart failure patients with a narrow QRS complex (<120 ms) undergoing CRT was included at two centres. Several widely accepted measures of mechanical dyssynchrony were evaluated: LV filling ratio (LVFT/RR), LV pre-ejection time (LPEI), interventricular mechanical dyssynchrony (IVMD), opposing wall delay (OWD), and anteroseptal posterior wall delay with speckle tracking (ASPWD). Response to CRT was defined as a reduction ≥15% in left ventricular end-systolic volume at 6 months follow-up. Measures of dyssynchrony can frequently be observed in patients with a narrow QRS complex. Nonetheless, for LVFT/RR, LPEI, and IVMD, presence of predefined significant dyssynchrony is <20%. Significant intraventricular dyssynchrony is more widely observed in these patients. With receiver operator characteristic curve analyses, both OWD and ASPWD demonstrated usefulness in predicting response to CRT in narrow QRS patients with a cut-off value of 75 and 107 ms, respectively., Conclusion: mechanical dyssynchrony can be widely observed in heart failure patients with a narrow QRS complex. In particular, intraventricular measures of mechanical dyssynchrony may be useful in predicting LV reverse remodelling at 6 months follow-up in heart failure patients with a narrow QRS complex, but with more stringent cut-off values than currently used in 'wide' QRS patients.

Aims: Cardiac resynchronization therapy (CRT) improves cardiac function, heart failure symptoms, and prognosis in selected patients. Many baseline characteristics associated with heart failure may influence prognosis after CRT. The objective of this study was to evaluate the effect of several baseline characteristics in relation to long-term prognosis in heart failure patients treated with CRT., Methods and Results: A total of 716 consecutive heart failure patients treated with CRT were included in an observational registry. All available data, including clinical and echocardiographic measurements, were analysed in relation to two endpoints: all-cause mortality and a combined endpoint of all-cause mortality or major cardiovascular event. Outcome data were collected by chart review, device interrogation, and telephone contact. Mean follow-up was 25 ± 19 months. During follow-up, 141 patients (20%) died (primary endpoint). Most of these patients (61%) died due to worsening heart failure. A total of 214 patients (30%) reached the secondary endpoint. Larger left ventricular end-systolic volume, less distance covered in the 6 min walking test, poor renal function, more severe heart failure, male gender, presence of atrial fibrillation, no posterolateral left ventricular (LV) lead, and no LV dyssynchrony were associated with poor prognosis after CRT., Conclusion: In this large single-centre registry, several baseline clinical and echocardiographic characteristics were associated with prognosis after CRT. Worsening heart failure was the main cause of death in heart failure patients treated with CRT.

Cardiac resynchronization therapy (CRT) is considered a class I indication in treatment of patients with New York Heart Association (NYHA) functional class III and IV heart failure. However, only small numbers of patients in large clinical trials have been in NYHA functional class IV. Therefore, little is known about the effects of CRT in this group. Therefore, we evaluated the effects of CRT in patients with NYHA functional class IV heart failure. Of all patients referred for CRT implantation, 61 patients with symptoms according to NYHA functional class IV were included. All patients were evaluated before implantation and at 6-month follow-up for clinical changes according to the clinical composite score and changes in left ventricular (LV) volumes and function. In addition, survival was evaluated during long-term follow-up. At 6-month follow-up, 9 patients (15%) had died and 2 patients (3%) were admitted for worsening heart failure. The remaining 39 patients (64%) showed improvement according to the clinical composite score. Decreases in LV end-systolic volume (from 167 ± 88 to 147 ± 93 ml, p = 0.009) and LV end-diastolic volume (from 211 ± 100 to 199 ± 113 ml, p = 0.135) were observed, as was a significant increase in LV ejection fraction (from 22 ± 8% to 28 ± 9%, p <0.001). During a mean follow-up of 30 ± 26 months, 36 patients (59%) died, 27 (75%) from worsening heart failure. Respective 1- and 2-year mortality rates were 25% and 38%. In conclusion, CRT decreases LV volumes and improves cardiac function in patients with NYHA functional class IV heart failure. Nevertheless, (heart failure) mortality remains high in these patients., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Aims: Heart failure and atrial fibrillation (AF) frequently coexist and AF worsens heart failure prognosis. Device-based diagnostics derived from implantable cardioverter-defibrillator (ICD) interrogation provide an accurate method for detecting AF episodes. This study sought to determine clinical and echocardiographic predictors of AF occurrence, including an index of total atrial conduction time derived by tissue Doppler imaging (PA-TDI duration), in patients with heart failure. Moreover, the role of PA-TDI duration on the prediction of AF occurrence in subgroups of patients with and without history of AF was explored., Methods and Results: A cohort of 495 heart failure patients who underwent ICD implantation was studied. Baseline echocardiographic parameters of systolic and diastolic function were evaluated together with clinical parameters. Furthermore, PA-TDI duration was measured. All patients were prospectively followed up after ICD implantation for AF occurrence detected by ICD interrogation. A total of 142 (29%) patients experienced AF over a follow-up period of 16.4 ± 11.2 months. PA-TDI duration was longer in patients with AF occurrence when compared with patients without AF occurrence (154 ± 27 vs. 135 ± 24 ms, P < 0.001). On Cox-multivariable analysis, female gender [hazard ratio = 1.60; 95% confidence intervals (CI) = 1.09-2.35; P = 0.017], history of AF (hazard ratio = 2.22; 95% CI, 1.51-3.27; P < 0.001), and PA-TDI duration (hazard ratio = 1.27; 95% CI, 1.13-1.42; P < 0.001) were independent predictors of AF occurrence. In the subgroups of patients with and without history of AF, PA-TDI duration remained an independent predictor of AF occurrence., Conclusion: PA-TDI duration may be useful to risk-stratify for AF occurrence in heart failure patients with and without a history of AF.

Background: Although most patients who improve in clinical status after cardiac resynchronization therapy (CRT) also show a significant left ventricular (LV) reverse remodeling, some patients do not show echocardiographic improvement. The aim of the present study was to evaluate the degree of agreement between clinical and echocardiographic response to CRT in a large cohort of heart failure patients, and to evaluate the characteristics of patients with clinical response but without echocardiographic response., Methods: In 440 consecutive heart failure patients (mean age 66 ± 11 years, 81% men) treated with CRT, agreement between clinical and echocardiographic responses at 6 months of follow-up were evaluated. The combined clinical response was defined as: ≥1-point New York Heart Association functional class improvement or ≥15% increase in 6-minute walk test. Echocardiographic response was defined by a reduction in LV end-systolic volume (LVESV) ≥15%., Results: At 6 months of follow-up, clinical response was observed in 84% (n = 370) of the patients. Significant reduction in LVESV was noted in 63% (n = 276). The majority of patients who improved clinically did show LV reverse remodeling (72%, n = 268). Importantly, 28% (n = 102) of patients who improved clinically did not show significant LV reverse remodeling. The patients with clinical response but without echocardiographic response had more often ischemic heart failure as compared to patients with positive clinical and echocardiographic response (69.6% vs 57.5%; P = .021). Moreover, patients with such discordant responses had more narrow QRS complex (148 ± 31 vs 159 ± 31 milliseconds; P = .004), and showed less LV dyssynchrony than patients with concordant positive responses (90 ± 77 vs 171 ± 105 milliseconds; P < .001)., Conclusions: Although there is a good concordance between echocardiographic and clinical response to CRT, up to 28% of the population experienced clinical response without significant LV reverse remodeling. Subjects with such discrepant responses have more frequently ischemic heart failure and show more narrow QRS complex and less LV dyssynchrony than patients with both clinical and echocardiographic response., (Copyright © 2010 Mosby, Inc. All rights reserved.)

The analysis of left ventricular (LV) mechanics provides novel insights into the effects of cardiac resynchronization therapy (CRT) on LV performance. Currently, advances in speckle-tracking echocardiographic analysis have permitted the characterization of subendocardial and subepicardial LV twist. The aim of this study was to investigate the role of the acute changes in subendocardial and subepicardial LV twist for the prediction of midterm beneficial effects of CRT. A total of 84 patients with heart failure scheduled for CRT were recruited. All patients underwent echocardiography before and <48 hours after CRT implantation and at 6-month follow-up. The assessment of LV volumes, ejection fractions, and mechanical dyssynchrony (systolic dyssynchrony index) was performed with real-time 3-dimensional echocardiography. The assessment of subendocardial and subepicardial LV twist was performed with 2-dimensional speckle-tracking echocardiography. A favorable outcome was defined as the occurrence of a reduction > or =15% in LV end-systolic volume associated with an improvement of > or =1 New York Heart Association functional class at 6-month follow-up. At 6-month follow-up, 53% of the patients showed favorable outcomes. Ischemic cause of heart failure, baseline systolic dyssynchrony index, immediate improvement in the LV ejection fraction, immediate improvement in systolic dyssynchrony index, and immediate improvement in subendocardial and subepicardial LV twist were significantly related to favorable outcomes. However, in multivariate logistic regression analysis, only the immediate improvement of subepicardial LV twist was independently related to favorable outcomes (odds ratio 2.31, 95% confidence interval 1.29 to 4.15, p = 0.005). Furthermore, the immediate improvement of subepicardial LV twist had incremental value over established parameters. In conclusion, the immediate improvement of subepicardial LV twist (but not subendocardial LV twist) is independently related to favorable outcomes after CRT., (2010 Elsevier Inc. All rights reserved.)

Cardiac resynchronization therapy (CRT) is an effective treatment for patients with drug-refractory, chronic heart failure. Multiple single-center and multicenter studies have shown significant reductions in left ventricular (LV) volumes and an increase in LV systolic function. More importantly, CRT reduces mortality and morbidity during long-term follow-up. Current guidelines consider CRT as a Class I indication for heart failure patients in New York Heart Association (NYHA) functional class III to IV with depressed LV ejection fraction or=120 ms). However, the benefits of this therapy could possibly be extended to selected subgroups of patients who do not fulfill these criteria. These subgroups include patients with mildly symptomatic heart failure and patients with a narrow QRS complex (<120 ms). Results from recent multicenter controlled clinical trials including heart failure patients in NYHA functional class I to II or with a narrow QRS complex are equivocal. Although expanding CRT to patients with a narrow QRS complex seems currently not likely, the benefits of CRT in mildly symptomatic patients are more evident. Perhaps attenuation of disease progression will prove to be a successful new treatment strategy in heart failure patients in the future. In addition, multimodality cardiac imaging will allow optimizing responder rate in patients undergoing CRT according to current guidelines., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)